Identifying imaging biomarkers of cognitive impairment in autoimmune encephalitis

Cleveland Clinic Lerner Com-Cwru, Cleveland OH

Investigators

Abstract

Project Summary Autoimmune limbic encephalitis (ALE) is an autoimmune disorder that involves inflammation of the brain, specifically the limbic region that processes memory. It is increasingly encountered by neurologists due to greater prevalence, recognition and diagnostics. It can be treated with immunosuppressive agents which improve acute symptoms of confusion and seizures. However, over the long-term, despite initial general improvement in severe symptoms, many patients do not fully recover and continue to experience residual symptoms, particularly impacting their cognition. Due to these chronic cognitive symptoms, many clinicians are faced with the dilemma of whether to continue immunosuppression or not. This is because it is unclear whether the basis of these cognitive symptoms are immune mediated or are due to structural or functional changes in the brain. Many patients with AE have normal appearing conventional brain MRI’s. We currently do not have good MRI biomarkers that demonstrate the changes that occur in people with ALE compared to healthy controls. We also do not know whether there are MRI biomarkers that associate with cognitive impairment in people with AE. There is a need to investigate whether novel MRI techniques can be identified that associate with cognitive impairment in AE. In MS and Alzheimer’s disease, novel MRI techniques such as diffusion tensor imaging (DTI) and resting state MRI (rs-fMRI) provide useful information about the structure and function of the brain, that is not visible on conventional MRI. These changes have been associated with cognitive impairment in these disorders. We anticipate that by using these novel MRI methods, we will identify structural and functional abnormalities that associate with cognitive impairment (specifically memory) and will provide insights into the basis of longitudinal cognitive impairment. This study leverages the existing strengths of the Cleveland Clinic including the large longitudinal cohort of patients with autoimmune encephalitis from which to recruit from. We have the infrastructure for advanced 7T MRI capabilities and translation research expertise with DTI and rs-fMRI. Finally, we have a robust healthy control cohort from the Cleveland Clinic brain study who are undergoing 7T MRI and neuropsychological testing as part of the study. This data will be available for a comparison. This study will be pivotal in understanding long-term cognitive outcomes in autoimmune encephalitis and the structural and functional features of this.